Expression of an anti-CD4 single chain antibody fragment from the donor cornea can prolong corneal allograft survival in inbred rats

Sarah Appleby, Claire Jessup, Lauren Mortimer, Kirsty Kirk, Helen Brereton, Douglas Coster, Chuan Tan, Keryn Williams

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    3 Citations (Scopus)

    Abstract

    Aim: To investigate whether expression of an anti-CD4 antibody fragment (scFv) by a lentivector-transduced donor cornea can prolong rat corneal allograft survival. Methods: Inbred Fischer 344 rats received penetrating corneal allografts from Wistar-Furth donors after a 3 h transduction of the donor cornea with a lentivector carrying anti-CD4scFv cDNA (Lv-CD4scFv), a lentivector carrying the reporter gene-enhanced yellow fluorescence protein (LV-eYFP), or an adenoviral vector carrying anti-CD4 scFv cDNA (Ad-CD4scFv). Unmodified controls were also performed. Graft survival was assessed by corneal clarity, and rejection was confirmed histologically. Results: In organ-cultured corneas, expression of anti-CD4 scFv was detected at 2 days post-transduction with the adenoviral vector, compared with 5 days post-transduction with the lentivector, and was 10-fold higher than the former. More inflammation was observed in Ad-CD4scFv-modified allografts than in Lv-CD4scFv-modified grafts at 15 days postsurgery ( p=0.01). The median time to rejection for unmodified, LV-eYFP and Ad-CD4scFv grafts was day 17, compared with day 22 for Lv-CD4scFv grafts (p≤0.018). Conclusion: Donor corneas transduced with a lentiviral vector carrying anti-CD4scFv cDNA showed a modest but significant prolongation in graft survival compared with unmodified, Lv-eYFP and Ad-CD4scFv grafts. However, rejection still occurred in all Lv-CD4scFv grafts, indicating that sensitisation may have been delayed but was not prevented.

    Original languageEnglish
    Pages (from-to)101-105
    Number of pages5
    JournalBritish Journal of Ophthalmology
    Volume97
    Issue number1
    DOIs
    Publication statusPublished - 2013

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